1083 CLOFIBRATE AND GALLSTONES SIR,—It has been shown that clofibrate can increase the lithogenicity of bile1 and predicted that gallstones may be The more common in patients treated with this drug. recent report of the Coronary Drug Project 2 indicates that, for patients with myocardial infarction treated with clofibrate, the 5-year incidence of gallstones was 3-0% compared with 1-3% in a control group-a significant increase. The problem has now been further assessed on the basis of data from the international cooperative trial of the primary prevention of ischasmic heart-disease using clofibrate.33 This trial is being carried out in healthy men aged 30-59. Three groups of equivalent size are included: two groups ’
FREQUENCY
OF
*
CHOLECYSTECTOMY
Information from only
FOR
two
this may represent 40-50 years. Very real difficulties in epidemiological survey therefore become apparent. It seems to me that a strong case can be argued for the establishment of central registers of diseases in the leukxmialymphoma group for prospective epidemiological survey. I would argue that these diseases should be made notifiable at time of diagnosis to a central authority. (Is this a publichealth matter ?) I appreciate the comments of Professor Bahn (Feb. 15, p. 393). It seems to me that the children with leukaemia, to whom I have been exposed, have been affectionate, bright youngsters, and to discourage closeness to such children by others or produce any element of public hysteria about this understandably raises negative feelings. ’
GALLSTONES IN THE COOPERATIVE TRIAL OF THE HEART-DISEASE USING CLOFIBRATE: JANUARY, 1975
of the three trial centres is included. Data from the third
with serum-cholesterol concentrations in the highest third of the distribution of cholesterol values determined at preliminary screening, and one group whose serumcholesterol concentrations were in the lowest third of the distribution. One of the high-serum-cholesterol groups was treated with clofibrate (1-6 g. per day), and the other with a placebo: the low-serum-cholesterol group was also treated with a placebo. The data in the accompanying table are consistent with the hypothesis that clofibrate can induce gallstones or, at least, initiate symptoms. The figures refer only to cholecystectomies undertaken for gallstones, because the incidence of gallstones could not be accurately assessed. The percentage affected in the clofibrate-treated group is more than twice that of either of the two control groups (p < 0-001). The rate does not therefore appear to be related to initial serum-cholesterol level.
PRIMARY
(Budapest)
PREVENTION
OF
ISCHI £ MIC .
are
being collected.
However, the letter by Dr Brody (Jan. 25, p. 223) may not be without foundation, and similar situations may have .
occurred in other investigators. As your editorial suggested, there may, however, be a bright side to the picture, if analogies between the feline and human situation can be made. The feasibility of vaccination against feline leukaemia has been demonstrated,l immunity to leukaemia in cats being directly related to the development of high titres of antibody to oncornavirus antigen in the cell membrane.2 In man, workers in Australia3 have detected the presence of high-avidity antibody in the membrane antigen-antibody complexes of long-term survivors of acute leukaemia, as distinct from those with a poorer prognosis. Perhaps vaccination in man may not be that far off! Suite 503-145, East 13th Street, North Vancouver, B.C. V7L 2L4, Canada.
JAMES E. PARKER.
Department of Community Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1.
JANE COOPER.
Cardiovascular Research Centre of the Institute for Clinical and
Experimental Medicine, 809 Budejovicka, Praha 4, Czechoslovakia. Department of Cardiology,
Royal Infirmary, Edinburgh EH3 9YW. For the
CHROMOSOMES AND MALIGNANCY SIR,—Ishould like to comment on the cytogenetic data in the interesting paper by Dr Canellos and others (April p. 947) concerning second malignancies complicating Hodgkin’s disease in remission. Amongst these were two leuksemic patients whose cells were interpreted as lacking a C-group chromosome, but because these studies antedated the introduction of the banding technique the karyotypes were not fully analysable. Such simple aneuploidy is a not uncommon feature of leukaemic cells of cases arising de novo, but cannot be attributed to the effect of ionising radiations or chemotherapeutic agents. Visible chromosomal changes produced by these agents are of the breakage/rearrangement type. With ionising irradiations, stable clones identified by deleted chromosomes may be produced in the bone-marrow-for example, in patients treated with 32P for pblycythaemia vera. No example has yet been recorded of the production of a stable clone with abnormal chromosomes in bone-marrow in a patient treated by chemotherapy alone, although there is no doubt that
26, HELENA GEIZEROVA. M. F. OLIVER.
Coordinating Committee of the W.H.O. Cooperative Trial.
EPIDEMIOLOGY OF LEUKÆMIA SIR,-A plea is made in your editorial of March 22 (p. 671) for better studies of the epidemiology of leukaemia in man. The analogy between the feline and the human situation, which had been elaborated in a preceding discussion (March 1, p. 503), highlights a very important point. A period of at least 8-10 years is necessary to test the possibility of transmission in a space-time cluster in cats. In terms of life-span relevant to the human situation,
2.
Jarrett, W., Mackay, L., Jarrett, O., Laird, H., Hood, C. Nature, 1974, 248, 230. Cotter, S. M., Essex, M., Hardy, W. D., Jr. Cancer Res. 1974, 34,
3.
Jose, D. G., Colebatch, J. H. Lancet, 1974, ii, 835.
1. 1. 2. 3.
Pertsemlidis, D., Panveliwalla, D., Ahrens, E. H. Gastroenterology, 1974, 66, 565. The Coronary Drug Project. J. Am. med. Ass. 1975, 231, 360. Heady, J. A. Bull. Wld Hlth Org. 1973, 48, 243.
1061.
FREQUENCY
OF
*
CHOLECYSTECTOMY
Information from only
FOR
two
this may represent 40-50 years. Very real difficulties in epidemiological survey therefore become apparent. It seems to me that a strong case can be argued for the establishment of central registers of diseases in the leukxmialymphoma group for prospective epidemiological survey. I would argue that these diseases should be made notifiable at time of diagnosis to a central authority. (Is this a publichealth matter ?) I appreciate the comments of Professor Bahn (Feb. 15, p. 393). It seems to me that the children with leukaemia, to whom I have been exposed, have been affectionate, bright youngsters, and to discourage closeness to such children by others or produce any element of public hysteria about this understandably raises negative feelings. ’
GALLSTONES IN THE COOPERATIVE TRIAL OF THE HEART-DISEASE USING CLOFIBRATE: JANUARY, 1975
of the three trial centres is included. Data from the third
with serum-cholesterol concentrations in the highest third of the distribution of cholesterol values determined at preliminary screening, and one group whose serumcholesterol concentrations were in the lowest third of the distribution. One of the high-serum-cholesterol groups was treated with clofibrate (1-6 g. per day), and the other with a placebo: the low-serum-cholesterol group was also treated with a placebo. The data in the accompanying table are consistent with the hypothesis that clofibrate can induce gallstones or, at least, initiate symptoms. The figures refer only to cholecystectomies undertaken for gallstones, because the incidence of gallstones could not be accurately assessed. The percentage affected in the clofibrate-treated group is more than twice that of either of the two control groups (p < 0-001). The rate does not therefore appear to be related to initial serum-cholesterol level.
PRIMARY
(Budapest)
PREVENTION
OF
ISCHI £ MIC .
are
being collected.
However, the letter by Dr Brody (Jan. 25, p. 223) may not be without foundation, and similar situations may have .
occurred in other investigators. As your editorial suggested, there may, however, be a bright side to the picture, if analogies between the feline and human situation can be made. The feasibility of vaccination against feline leukaemia has been demonstrated,l immunity to leukaemia in cats being directly related to the development of high titres of antibody to oncornavirus antigen in the cell membrane.2 In man, workers in Australia3 have detected the presence of high-avidity antibody in the membrane antigen-antibody complexes of long-term survivors of acute leukaemia, as distinct from those with a poorer prognosis. Perhaps vaccination in man may not be that far off! Suite 503-145, East 13th Street, North Vancouver, B.C. V7L 2L4, Canada.
JAMES E. PARKER.
Department of Community Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1.
JANE COOPER.
Cardiovascular Research Centre of the Institute for Clinical and
Experimental Medicine, 809 Budejovicka, Praha 4, Czechoslovakia. Department of Cardiology,
Royal Infirmary, Edinburgh EH3 9YW. For the
CHROMOSOMES AND MALIGNANCY SIR,—Ishould like to comment on the cytogenetic data in the interesting paper by Dr Canellos and others (April p. 947) concerning second malignancies complicating Hodgkin’s disease in remission. Amongst these were two leuksemic patients whose cells were interpreted as lacking a C-group chromosome, but because these studies antedated the introduction of the banding technique the karyotypes were not fully analysable. Such simple aneuploidy is a not uncommon feature of leukaemic cells of cases arising de novo, but cannot be attributed to the effect of ionising radiations or chemotherapeutic agents. Visible chromosomal changes produced by these agents are of the breakage/rearrangement type. With ionising irradiations, stable clones identified by deleted chromosomes may be produced in the bone-marrow-for example, in patients treated with 32P for pblycythaemia vera. No example has yet been recorded of the production of a stable clone with abnormal chromosomes in bone-marrow in a patient treated by chemotherapy alone, although there is no doubt that
26, HELENA GEIZEROVA. M. F. OLIVER.
Coordinating Committee of the W.H.O. Cooperative Trial.
EPIDEMIOLOGY OF LEUKÆMIA SIR,-A plea is made in your editorial of March 22 (p. 671) for better studies of the epidemiology of leukaemia in man. The analogy between the feline and the human situation, which had been elaborated in a preceding discussion (March 1, p. 503), highlights a very important point. A period of at least 8-10 years is necessary to test the possibility of transmission in a space-time cluster in cats. In terms of life-span relevant to the human situation,
2.
Jarrett, W., Mackay, L., Jarrett, O., Laird, H., Hood, C. Nature, 1974, 248, 230. Cotter, S. M., Essex, M., Hardy, W. D., Jr. Cancer Res. 1974, 34,
3.
Jose, D. G., Colebatch, J. H. Lancet, 1974, ii, 835.
1. 1. 2. 3.
Pertsemlidis, D., Panveliwalla, D., Ahrens, E. H. Gastroenterology, 1974, 66, 565. The Coronary Drug Project. J. Am. med. Ass. 1975, 231, 360. Heady, J. A. Bull. Wld Hlth Org. 1973, 48, 243.
1061.
